Particle flow numerical simulation model for coal and gas outburst and its microscopic outburst mechanism description.

The finite difference model and particle flow model were constructed to reproduce the process of coal and gas outburst in front of the tunnel. The reliability of the particle flow model was verified by studying the internal stress, gas pressure, and related parameters of gas and coal two-phase flow. Then the process of coal and gas outburst is described from a microscopic perspective. The results show that the particle flow numerical model of coal and gas outburst is in line with reality and can intuitively and conveniently monitor relevant parameters; The concentrated stress caused by excavation of tunnels can reach 1.2 times the in-situ stress; High stress causes the adhesion between coal particles to break down, which is the main reason for the initiation of coal and gas outbursts; The intermittent breakthrough of gas on the coal particle collection that blocks the release channel has caused pulsating characteristics of coal and gas outbursts.

Mechanistic and Kinetic Consideration of the Photochemically Generated Oxidative Organic Radicals in Dissolved Black Carbon Solutions under Simulated Solar Irradiation.

The photochemically generated oxidative organic radicals (POORs) in dissolved black carbon (DBC) was investigated and compared with that in dissolved organic matter (DOM). POORs generated in DBC solutions exhibited higher one-electron reduction potential values (1.38-1.56 V) than those in DOM solutions (1.22-1.38 V). We found that the photogeneration of POORs from DBC is enhanced with dissolved oxygen (DO) increasing, while the inhibition of POORs is observed in reference to DOM solution. The behavior of the one-electron reducing species (DBC•-/DOM•-) was employed to explain this phenomenon. The experimental results revealed that the DO concentration had a greater effect on DBC•- than on DOM•-. Low DO levels led to a substantial increase in the steady-state concentration of DBC•-, which quenched the POORs via back-electron reactions. Moreover, the contribution of POORs to the degradation of 19 emerging organic contaminants (EOCs) in sunlight-exposed DBC and DOM solutions was estimated. The findings indicate that POORs play an important role in the photodegradation of EOCs previously known to react with triplets, especially in DBC solutions. Compared to DOM solutions, POOR exhibits a lower but considerable contribution to EOC attenuation. This study enhances the understanding of pollutant fate in aquatic environments by highlighting the role of DBC in photochemical pollutant degradation and providing insights into pollutant transformation mechanisms involving POORs.

Prediction method of coal mine gas occurrence law based on multi-source data fusion.

To improve the prediction accuracy and time-consuming of coal mine gas occurrence law (OL), a new prediction method based on multi-source data fusion is proposed in this paper. Firstly, the method obtains the data of coal mine gas OL, determines the key data required in prediction through decision matrix, and preprocesses the data to reduce the influence of regular noise data. This paper analyzes the basic principle of multi-source data fusion, constructs the prediction model of coal mine gas OL with this technology, takes the optimal value of weighting factor as the input value of the model, and completes the design of coal mine gas OL prediction method based on multi-source data fusion. The experimental results show that the accuracy of this method can reach 98%, while that of the other two traditional methods is lower than the existing methods. This method has high accuracy and efficiency in predicting the coal mine gas OL.

Trends in cardiovascular risk factors control among US adults by glycemic statuses, 2007-2018.

AIMS: Understanding the national trends in cardiovascular risk factors control of individuals with prediabetes and diabetes is critical for diabetes prevention and management. Our study aims to estimate how cardiovascular risk factors changed in US adults with different glycemic statuses between 2007-2008 and 2017-2018. METHODS AND RESULTS: This was a serial cross-sectional study based on the National Health and Nutrition Examination Surveys (between 2007-2008 and 2017-2018 cycle). Non-pregnant American participants aged 20 years or older were included. Cardiovascular risk factors including weight, blood pressure, plasma cholesterol, and smoking by glycemic statuses were estimated. A total of 33 040 American adults were included. From 2007-2008 to 2017-2018, the age-adjusted proportions of individuals who reached weight control (body mass index <30 kg/m2) of both normoglycemia group and prediabetes group had a significant decrease over the study period, while the trend in participants with diabetes was not significant (mean difference: -5.34%, 95% confidence interval: -15.28%, 4.59%; P for trend = 0.298). The age-adjusted means of total cholesterol of all three groups decreased during the study decade (P for trend < 0.010), with participants with diabetes maintaining the lowest level. Individuals with high total cholesterol were more likely to receive statin therapy in the diabetes group. Notably, prediabetes participants had the highest level of total cholesterol and low-density lipoprotein cholesterol and were less likely to achieve lipid control with statin therapy. Sensitivity analysis with the second definition of prediabetes and diabetes resulted in a consistent trend. CONCLUSIONS: In this nationally representative cross-sectional study, we systematically estimated the cardiovascular risk factors control in American adults and found poor weight control in the normoglycemia and prediabetes group. Despite the significant decrease trend of plasma total cholesterol in all groups, the high cholesterol level in the prediabetes group deserves special concern.

This work mapped the changes in key cardiovascular risk factors control of the general US adults with different glycemic statuses from 2007 to 2018. Weight, blood pressure, and smoking control had not significantly improved in American adults with different glycemic statuses. Plasma cholesterol levels had decreased over the study period, but the poor lipid control in the prediabetes group deserves special attention.

Time Trends of Ventricular Reconstruction and Outcomes among Patients with Left Ventricular Thrombus and Aneurysms.

Background: Clinical guidelines recommend surgical intervention when left ventricular thrombus (LVT) is complicated with left ventricular aneurysm (LVA). Objectives: This study aimed to review the changes in the treatment of LVT combined with LVA over the past 12 years at our center and to compare the efficacy of medical therapy and surgical treatment on patient outcomes. Methods: Between January 2009 and June 2021, 723 patients with LVT combined with LVA were enrolled, of whom 205 received surgical ventricular reconstruction (SVR) therapy and 518 received medical therapy. The following clinical outcomes were gathered via observation: all-cause death, cardiovascular death, and major adverse cardiovascular and cerebrovascular events (MACCEs; defined as the composite of cardiovascular death, ischemic stroke, and acute myocardial infarction). The median follow-up time was 1403 [707, 2402] days. Results: The proportion of SVR dropped yearly in this group of patients, from a peak of 64.5% in 2010 to 7.5% in 2021 (p for trend < 0.001). Meanwhile, the proportion of anticoagulant use increased quickly, from 8.0% in 2016 to 67.9% in 2021 (p for trend < 0.001). The incidence rates of all-cause mortality, cardiovascular death, and MACCEs were 12.9% (n = 93), 10.5% (n = 76), and 14.7% (n = 106), respectively. In the multivariable analysis, there were no significant differences in all-cause death (HR of 0.60, 95% CI of 0.32−1.13, p = 0.11), cardiovascular death (HR of 0.79, 95% CI of 0.41−1.50, p = 0.5), and MACCEs (HR of 0.82, 95% CI of 0.49−1.38, p = 0.5) between the two groups. The competing risk regression performed in the propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses was in line with the unmatched analysis. Conclusions: The rate of SVR dropped significantly among patients with both LVT and LVA, while there was an improvement in oral anticoagulant utilization. SVR with thrombus removal did not improve all-cause mortality and cardiovascular outcomes in patients with LVT and LVA. Ventricular aneurysm with thrombus may not be an indication for surgery.

Analysis of the Bacterial Spectrum and Key Clinical Factors of Biliary Tract Infection in Patients with Malignant Obstructive Jaundice after PTCD.

Objective: To analyze the bacterial spectrum and key clinical factors associated with biliary tract infections following percutaneous transhepatic cholangial drainage (PTCD) for malignant obstructive jaundice (MOJ). Methods: This retrospective study comprised patients with MOJ who were treated with PTCD from 1st June 2016 to 31st December 2020. Patient clinical data, development of postprocedure biliary tract infections, spectrum of pathogenic bacteria, and drug sensitivity were analyzed, focusing on antibiotic drug resistance and identifying key associated risk factors for postoperative biliary tract infections. Results: Of the 528 study patients, 80 were diagnosed with postoperative biliary tract infections, 58 of whom had pathogenic bacteria detected in their bile samples. A total of 90 strains of pathogenic bacteria and 3 strains of fungi were detected; the top 4 were Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, and Pseudomonas aeruginosa. By univariate analysis, a positive bile culture following PTCD was closely correlated with both the location and degree of preoperative obstruction and the preoperative bilirubin level. Moreover, the results of logistic regression analysis concluded that complete obstruction and a high preoperative total bilirubin level prior to PTCD were independent risk factors for a positive bile culture following PTCD. Conclusion: Biliary tract infections following PTCD for MOJ were principally due to Escherichia coli, and bacteria in the bile were statistically more likely to be detected in patients with complete obstruction and high preoperative bilirubin levels.

Recent Studies on Hydrogels Based on H2O2-Responsive Moieties: Mechanism, Preparation and Application.

H2O2 is essential for cellular processes and plays a vital role in the regulation of cell signaling pathways, which can be viewed as a warning signal for many kinds of disease including cancer, cardiovascular disease, reproductive abnormalities, diabetes, and renal failure. A H2O2-responsive hydrogel (H2O2-Gel) is a promising candidate for biomedical applications because of its good biocompatibility, similarity to soft biological tissues, ease of preparation, and its ability to respond to H2O2. In this study, the H2O2-responsive moieties used to fabricate H2O2-Gels were reviewed, including thioethers, disulfide bonds, selenides, diselenium bonds, diketones, boronic, and others. Next, the preparation method of H2O2-Gel was divided into two major categories according to their reaction mechanisms: either self-crosslinking or mechanisms entailing the addition of difunctional crosslinkers. Last, the applications of H2O2-Gels were emphasized, which have been viewed as desirable candidates in the fields of drug delivery, the detection of H2O2, glucose-responsive systems, ROS scavengers, tissue engineering, and cell-encapsulation.

Non-targeted analysis for organic components of microplastic leachates.

Organic components of microplastic leachates were investigated in an integrated non-targeted analysis study that included statistical analysis on leachates generated under different leaching scenarios. Leaching experiments were undertaken with simulated gastric fluid (SGF), river water, and seawater with common polymer types, including polyethylene, polypropylene, polyvinyl chloride, polyethylene terephthalate, and polyester fabrics comprising both raw and recycled materials. Totals of 111.0 ± 26.7, 98.5 ± 20.3, and 53.5 ± 4.7 different features were tentatively identified as compounds in SGF, freshwater, and seawater leachates, respectively, of which 5 compounds were confirmed by reference standards. The leaching capacities of the media were compared, and the clusters of structurally related features leached in the same medium were studied. For leachates generated from raw and recycled plastics, volcano plots and Pearson's Chi-squared tests were used to identify characteristic features. More characteristic features (3-20) had an average intensity across all recycled plastics that were significantly higher (p < 0.05) than that (1-3) of raw plastics under different conditions. The results indicate that gastric solution is more likely to leach components from microplastics, and there exists the difference of leachate's organic composition between raw and recycled materials, providing new insights into understanding microplastic environmental effects.

The Effect of a WeChat-Based Tertiary A-Level Hospital Intervention on Medication Adherence and Risk Factor Control in Patients With Stable Coronary Artery Disease: Multicenter Prospective Study.

BACKGROUND: In China, ischemic heart disease is the main cause of mortality. Having cardiac rehabilitation and a secondary prevention program in place is a class IA recommendation for individuals with coronary artery disease. WeChat-based interventions seem to be feasible and efficient for the follow-up and management of chronic diseases. OBJECTIVE: This study aims to evaluate the effectiveness of a tertiary A-level hospital, WeChat-based telemedicine intervention in comparison with conventional community hospital follow-up on medication adherence and risk factor control in individuals with stable coronary artery disease. METHODS: In this multicenter prospective study, 1424 patients with stable coronary artery disease in Beijing, China, were consecutively enrolled between September 2018 and September 2019 from the Fuwai Hospital and 4 community hospitals. At 1-, 3-, 6-, and 12-month follow-up, participants received healthy lifestyle recommendations and medication advice. Subsequently, the control group attended an offline outpatient clinic at 4 separate community hospitals. The intervention group had follow-up visits through WeChat-based telemedicine management. The main end point was medication adherence, which was defined as participant compliance in taking all 4 cardioprotective medications that would improve the patient's outcome (therapies included antiplatelet therapy, ß-blockers, statins, and angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers). Multivariable generalized estimating equations were used to compare the primary and secondary outcomes between the 2 groups and to calculate the relative risk (RR) at 12 months. Propensity score matching and inverse probability of treatment weighting were performed as sensitivity analyses, and propensity scores were calculated using a multivariable logistic regression model. RESULTS: At 1 year, 88% (565/642) of patients in the intervention group and 91.8% (518/564) of patients in the control group had successful follow-up data. We matched 257 pairs of patients between the intervention and control groups. There was no obvious advantage in medication adherence with the 4 cardioprotective drugs in the intervention group (172/565, 30.4%, vs 142/518, 27.4%; RR 0.99, 95% CI 0.97-1.02; P=.65). The intervention measures improved smoking cessation (44/565, 7.8%, vs 118/518, 22.8%; RR 0.48, 95% CI 0.44-0.53; P<.001) and alcohol restriction (33/565, 5.8%, vs 91/518, 17.6%; RR 0.47, 95% CI 0.42-0.54; P<.001). CONCLUSIONS: The tertiary A-level hospital, WeChat-based intervention did not improve adherence to the 4 cardioprotective medications compared with the traditional method. Tertiary A-level hospital, WeChat-based interventions have a positive effect on improving lifestyle, such as quitting drinking and smoking, in patients with stable coronary artery disease and can be tried as a supplement to community hospital follow-up. TRIAL REGISTRATION: ClinicalTrials.gov NCT04795505; https://clinicaltrials.gov/ct2/show/NCT04795505.

Sleep quality and risk of cancer: findings from the English longitudinal study of aging.

STUDY OBJECTIVE: To prospectively examine the association between sleep quality and incident cancer risk in the elderly. METHODS: A total of 10,036 participants aged ≥50 years free of cancer at baseline from the English Longitudinal Study of Ageing at wave 4 (2008) were included, and followed up until 2016. The primary endpoint was new onset physician-diagnosed cancer. Sleep quality was assessed by four questions regarding the frequency of sleep problems and overall subjective feeling of sleep quality in the last month, with higher score denoting poorer sleep quality. The multivariable Cox regression model was used to calculate hazard ratio (HR) with 95% confidence interval (CI) for incident cancer risk according to sleep quality. RESULTS: At 8-year follow-up, a total of 745 (7.4%) participants developed cancer. Compared with good sleep quality at baseline, HR (95% CI) for incident cancer risk was 1.328 (1.061, 1.662) for intermediate quality, 1.586 (1.149, 2.189) for poor quality. Similarly, compared with maintaining good sleep quality in the first 4 years, HR (95% CI) for incident cancer risk was 1.615 (1.208, 2.160) for maintaining intermediate quality and 1.608 (1.043, 2.480) for maintaining poor quality. The exclusion of participants with family history of cancer or abnormal sleep duration yielded consistent results. CONCLUSIONS: Poor sleep quality is positively associated with the long-term risk of developing cancer in an elderly cohort. Both medical staffs and the general public should pay more attention to improving sleep hygiene.

Reevaluation of the contributions of reactive intermediates to the photochemical transformation of 17ß-estradiol in sewage effluent.

Photodegradation of the natural steroid 17ß-estradiol (E2), an endocrine-disrupting hormone that has been widely detected in aquatic environments, was investigated in wastewater effluents at various pH ranges under simulated solar irradiation. The rate of E2 degradation in the sewage effluents was stable at pH 6.0-7.0 but suddenly increased from pH 8.0-10.0. The second-order reaction rate constants of E2 with 3EfOM* and CO3•- were measured to increase 11.0-fold and 18.0-fold from pH 6.0 to 10.0, respectively. Two main reasons are proposed for this sharp increase. First, the change in the ionization state of E2 made it susceptible to oxidation by triplet-state effluent organic matter (3EfOM*) and carbonate radicals (CO3•-). Second, the steady-state concentration of CO3•- increased with increasing pH. Indirect photolysis was suggested to be the main degradation pathway in the sewage effluents, and 3EfOM* was proposed to play a major role at pH 8.0-9.0, while CO3•- played a significant role at pH 10.0. In this study, EfOM was shown for the first time to inhibit the oxidation of E2 initiated by 3EfOM* and CO3•-. Thus, we suggest that EfOM plays a dual role in the photodegradation of E2: EfOM can not only be activated as 3EfOM* to degrade E2 but also can inhibit the degradation of E2 by reducing the E2 oxidation intermediate back to E2. The estrogenic activity of the photodegradation products was also studied. The in vitro estrogenic activity of E2 solutions decreased approximately as fast as the E2 photodegradation occurred in the effluent water at various pH values, suggesting that solar photodegradation in sewage effluents reduces the risk of endocrine disruption in waters impacted by E2 and subject to continuing inputs. The results of this study are important for predicting the environmental fate of endocrine-disrupting chemicals and developing methods for their removal from aquatic environments.

Therapeutic Targeting of Interleukin-11 Signalling Reduces Pressure Overload-Induced Cardiac Fibrosis in Mice.

There are currently no specific treatments for cardiac fibrosis. We tested the efficacy of a neutralising anti-IL11 antibody (X203) to reduce cardiac fibrosis in two preclinical models: transverse aortic constriction (TAC) and chronic angiotensin II infusion (AngII). In the first model, male C57BL/6J mice were subjected to TAC for 2 weeks. In the second model, mice received continuous angiotensin II for 4 weeks via subcutaneous pump. In both models, mice received either 20 mg/kg of X203 or isotype-control antibody twice-weekly, starting 24 h after surgery. Cardiac fibrosis and extracellular matrix gene expression were assessed by RT-qPCR, Western blot, histology and collagen (hydroxyproline) assays. In both models, X203 significantly reduced pro-fibrotic gene expression and myocardial fibrosis (TAC: 51% reduction in total collagen, P < 0.001, 39% in perivascular fibrosis, P < 0.001; AngII: 17% reduction in total collagen, P = 0.04, 83% in perivascular fibrosis, P < 0.001). Pharmacological targeting of IL11 reduces cardiac fibrosis in preclinical models. Figa Graphical Abstract.

YAP/TAZ deficiency reprograms macrophage phenotype and improves infarct healing and cardiac function after myocardial infarction.

Adverse cardiac remodeling after myocardial infarction (MI) causes structural and functional changes in the heart leading to heart failure. The initial post-MI pro-inflammatory response followed by reparative or anti-inflammatory response is essential for minimizing the myocardial damage, healing, and scar formation. Bone marrow-derived macrophages (BMDMs) are recruited to the injured myocardium and are essential for cardiac repair as they can adopt both pro-inflammatory or reparative phenotypes to modulate inflammatory and reparative responses, respectively. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the key mediators of the Hippo signaling pathway and are essential for cardiac regeneration and repair. However, their functions in macrophage polarization and post-MI inflammation, remodeling, and healing are not well established. Here, we demonstrate that expression of YAP and TAZ is increased in macrophages undergoing pro-inflammatory or reparative phenotype changes. Genetic deletion of YAP/TAZ leads to impaired pro-inflammatory and enhanced reparative response. Consistently, YAP activation enhanced pro-inflammatory and impaired reparative response. We show that YAP/TAZ promote pro-inflammatory response by increasing interleukin 6 (IL6) expression and impede reparative response by decreasing Arginase-I (Arg1) expression through interaction with the histone deacetylase 3 (HDAC3)-nuclear receptor corepressor 1 (NCoR1) repressor complex. These changes in macrophages polarization due to YAP/TAZ deletion results in reduced fibrosis, hypertrophy, and increased angiogenesis, leading to improved cardiac function after MI. Also, YAP activation augmented MI-induced cardiac fibrosis and remodeling. In summary, we identify YAP/TAZ as important regulators of macrophage-mediated pro-inflammatory or reparative responses post-MI.

Triplet Photochemistry of Dissolved Black Carbon and Its Effects on the Photochemical Formation of Reactive Oxygen Species.

Dissolved black carbon (DBC) is an important component of dissolved organic matter pool; however, its photochemical properties are not fully understood. In this study, we determined the excited triplet-state quantum yields of DBC (3DBC*) and 1O2 quantum yields (Φ1O2) of six diverse DBCs using sorbic alcohol, 2,4,6-trimethylphenol (TMP), and furfuryl alcohol and compared the results with quantum yields of reference natural organic matters (NOMs). The average Φ1O2 of six DBCs (4.2 ± 1.5%) was greater than that of terrestrial NOM (2.4 ± 0.3%) and comparable to autochthonous NOM (5.3 ± 0.2%). Using TMP as a probe for oxidizing triplets, DBC presented significantly higher apparent quantum yield coefficients for degrading TMP (fTMP) than the reference NOM, reflecting that the fTMP values of low-energy 3DBC* were approximately 12-fold greater than those of low-energy 3NOM*. The differences in the fTMP and Φ1O2 trends among the DBCs indicated that the 3DBC* responsible for these reactions may be from different sources. In addition, DBC was much more effective than NOM, on a carbon-normalized basis, during photodegradation of pharmaceutically active compounds. This result confirms that the presence of DBC can accelerate the photodegradation of contaminants that are susceptible to one-electron oxidation by triplets.

Collaborative Regulation of LRG1 by TGF-ß1 and PPAR-ß/δ Modulates Chronic Pressure Overload-Induced Cardiac Fibrosis.

BACKGROUND: Despite its established significance in fibrotic cardiac remodeling, clinical benefits of global inhibition of TGF (transforming growth factor)-ß1 signaling remain controversial. LRG1 (leucine-rich-α2 glycoprotein 1) is known to regulate endothelial TGFß signaling. This study evaluated the role of LRG1 in cardiac fibrosis and its transcriptional regulatory network in cardiac fibroblasts. METHODS: Pressure overload-induced heart failure was established by transverse aortic constriction. Western blot, quantitative reverse transcription polymerase chain reaction, immunofluorescence, and immunohistochemistry were used to evaluate the expression level and pattern of interested targets or pathology during fibrotic cardiac remodeling. Cardiac function was assessed by pressure-volume loop analysis. RESULTS: LRG1 expression was significantly suppressed in left ventricle of mice with transverse aortic constriction-induced fibrotic cardiac remodeling (mean difference, -0.00085 [95% CI, -0.0013 to -0.00043]; P=0.005) and of patients with end-stage ischemic-dilated cardiomyopathy (mean difference, 0.13 [95% CI, 0.012-0.25]; P=0.032). More profound cardiac fibrosis (mean difference, -0.014% [95% CI, -0.029% to -0.00012%]; P=0.048 for interstitial fibrosis; mean difference, -1.3 [95% CI, -2.5 to -0.2]; P=0.016 for perivascular fibrosis), worse cardiac dysfunction (mean difference, -2.5 ms [95% CI, -4.5 to -0.4 ms]; P=0.016 for Tau-g; mean difference, 13% [95% CI, 2%-24%]; P=0.016 for ejection fraction), and hyperactive TGFß signaling in transverse aortic constriction-operated Lrg1-deficient mice (mean difference, -0.27 [95% CI, -0.47 to -0.07]; P<0.001), which could be reversed by cardiac-specific Lrg1 delivery mediated by adeno-associated virus 9. Mechanistically, LRG1 inhibits cardiac fibroblast activation by competing with TGFß1 for receptor binding, while PPAR (peroxisome proliferator-activated receptor)-ß/δ and TGFß1 collaboratively regulate LRG1 expression via SMRT (silencing mediator for retinoid and thyroid hormone receptor). We further demonstrated functional interactions between LRG1 and PPARß/δ in cardiac fibroblast activation. CONCLUSIONS: Our results established a highly complex molecular network involving LRG1, TGFß1, PPARß/δ, and SMRT in regulating cardiac fibroblast activation and cardiac fibrosis. Targeting LRG1 or PPARß/δ represents a promising strategy to control pathological cardiac remodeling in response to chronic pressure overload.

Review-Novel synthetic curcuminoids: Not merely an anticancer agent.

Curcumin, a natural polyphenolic compound derived from turmeric (Curcuma longa L), has proven to exhibit biological activity towards different kinds of diseases. But the low oral bioavailability results in a limited application in clinic treatment. Recently, numerous curcumin derivatives were synthesized by the modification of three important functional groups: The aromatic o-methoxy phenolic group, a seven conjugated carbon linker and the ß-diket one moiety. However, many people know curcumin only as an anticancer agent and overlook the diverse biological activities of curcumin and curcumin-based derivatives. In this article, we summarized the novel synthetic curcuminoids by different therapeutic activities including antioxidant activity, anti-HIV activity, stimulating activity of gastric emptying, anti-inflammatory activity, ACE inhibition activity, prevention of Parkinson's disease, anti-parasitism, anti-obesity, prevention of Alzheimer's disease, and antibacterial activity. The relation between structural features and activities were also investigated.

Validating the Performance of 5 Risk Scores for Major Adverse Cardiac Events in Patients Who Achieved Complete Revascularization After Percutaneous Coronary Intervention.

BACKGROUND: Risk scores, like the Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (SS), clinical SS, logistic SS (core model and extended model [LSSextended]), Age, Creatinine, and Ejection Fraction (ACEF) score, and modified ACEF score, are predictive for major adverse cardiac events (MACE; including all-cause mortality, myocardial infarction [MI], and revascularization) in patients who have undergone percutaneous coronary intervention (PCI). However, few studies have validated the performance of these scores in complete revascularization (CR) patients. We aimed to compare the performance of previous risk scores in patients who achieved CR after PCI. METHODS: All patients (N = 10,724) who underwent PCI at Fuwai Hospital in 2013 were screened, and those who achieved CR after PCI were enrolled. Risk scores were calculated by experienced cardiologists blinded to the clinical outcomes. Discrimination of risk scores was assessed according to the area under the receiver operating characteristic curve (AUC). RESULTS: Fifty-one percent (5375/10,724) of patients who underwent PCI achieved CR. At a mean follow-up of 2.4 years, the mortality, MI, revascularization, and MACE rates were 1.2%, 1.0%, 6.3%, and 7.7%, respectively. SS was not predictive for mortality (AUC, 0.51; 95% confidence interval [CI], 0.44-0.59). All scores involving clinical variables, especially modified ACEF score (AUC, 0.73; 95% CI, 0.66-0.79), could predict mortality. LSSextended was the most accurate for MI (AUC, 0.68; 95% CI, 0.61-0.75). SS and LSSextended were predictive for revascularization, with marginally significant AUCs (SS, 0.54; LSSextended, 0.55). No score was particularly accurate for predicting MACE, with AUCs ranging from 0.51 (ACEF score) to 0.58 (LSSextended). CONCLUSIONS: In CR patients, risk scores involving clinical variables might help to predict mortality; however, no risk scores showed helpful discrimination for MACE.

Occurrence and estrogenic activity of steroid hormones in Chinese streams: A nationwide study based on a combination of chemical and biological tools.

Steroid hormones (SHs) are continuously released into the aquatic environment through various pathways after being excreted by humans and animals, interfere with the normal function of the endocrine system and may affect the physiology and reproduction of exposed aquatic life. To conduct a nationwide investigation of the occurrence and biological effects of SHs in surface river/steam water in China, we quantitated 27 selected SHs in 217 surface water samples by solid-phase extraction (SPE) tandem LC-MS/MS and used a recombinant yeast estrogen assay to screen extracts of the water samples for estrogenic activities. SHs were commonly found in the surface water samples, and their levels were typically in the ng L-1 range. Estrone (E1) and estriol (E3) were normally present in several to dozens of times higher concentrations than estradiol (E2) and 17-a-Ethinylestradiol (EE2). The high concentrations (mean > 1 µg L-1) of SumSHs were primarily obtained in areas under extreme water stress, specifically the eastern coastal areas. Source apportionment based on the profiles of the target compounds indicated that 54.5% of the SHs in target samples came from freshly discharged untreated sewage. The estrogen equivalent (EEQ(bio)) values ranged from 0.01 to 40.27 ng L-1, and the calculated EEQ (EEQ(cal)) values were generally lower than the corresponding EEQ(bio) values for all samples. E2 was the main contributor to the estrogenicity among the three estrogens, with a contribution ratio of 82.8%. The risk quotient values of E2 were highest and ranged from 1.55 to 782.95, and 76.0% of the target surface samples displayed the greatest environmental risk. We concluded that the impacts of SHs on humans in Chinese surface waters should not be ignored and that certain actions should be taken to decrease the levels of SHs in source waters, especially measures targeting SHs in untreated wastewater from the vast rural areas.

Photochemical Transformation of Nicotine in Wastewater Effluent.

Nicotine is a highly toxic tobacco alkaloid that is ubiquitous in wastewater effluent. For the first time, we report the identification of the products and the pathways for the photodegradation of nicotine in an effluent matrix under simulated solar irradiation. Nicotine was found to be degraded by triplet-state organic matter (3OM*), thus indicating that electron transfer is a preferred reaction mechanism. Using the multivariate statistical strategies orthogonal projection to latent structures discriminant analysis (OPLS-DA) and hierarchical clustering, 49 potential transformation products (TPs) of nicotine were successfully extracted from the water matrix via high-resolution ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). Overall, 30 TPs, including 4 groups of nonseparated isomeric photo TPs, were identified with various levels of confidence based on the tandem mass spectrometry information on standard compounds and the isotope-labeling method (using rac-nicotine-2',3',3'-D3, rac-nicotine-13CD3, and rac-nicotine-D4) under air-saturated conditions. The pyrrolidine ring of nicotine was found to be the reactive site under sunlight irradiation. Pseudooxynicotine was the main primary TP from nicotine, with a maximum transformation ratio of 64%. Nicotinic acid, cotinine, 3'-hydroxycotinine, and myosmine were the final stable TPs after 72 h of solar irradiation, with yields of 13%, 3%, 5%, and 5%, respectively.

A new target for differentiation therapy in AML.

Despite major advances in understanding the genetics and epigenetics of acute myelogenous leukemia, there is still a great need to develop more specific and effective therapies. High throughput approaches involving either genetic approaches or small molecule inhibitor screens are beginning to identify promising new therapeutic targets.